Effects of an extreme natural disaster on immunity and aging

项目摘要 极端不利的环境事件，如大飓风，与发病率增加有关， 无数健康问题的严重性。有趣的是，这些疾病中的许多在老年人中也更普遍。 暗示逆境和衰老以类似的方式影响免疫系统。综合来看，这表明 不良经历可能会加速免疫系统老化。免疫基因调控的中断可以 持续多年，预计将成为一个特别突出的机制， 灾害导致与衰老相关的健康状况下降。此外，个体在他们的生活中表现出广泛的异质性。 对逆境的反应，以及社会逆境等因素（即，社会经济地位、社会融合）， 实际年龄和性别与灾害后不同的健康结果有关。但大多数 迄今为止的研究都集中在没有基线数据的机会性收集样本上， 研究了极端飓风是否会加速基因表达和DNA甲基化以及如何加速 社会经验、实际年龄和性别影响免疫基因调节和衰老的多个领域。 拟议研究的目标是通过利用无与伦比的 来自圣地亚哥岛的恒河猴（Macaca mulatta）样本最近经历了 飓风玛丽亚猕猴是转化人类衰老研究的成熟动物模型， 它们与人类有许多共同的遗传，社会和免疫学特征。外周全血样本， 每年从青少年和成年雄性和雌性猕猴的代表性样品中收集RNA， 2014年至2016年飓风玛丽亚之前三年和之后一年（2018年）。血液样本DNA 从2010-2016年和2018年收集。我将利用这个独特的机会来调查 飓风玛丽亚及其对外周免疫系统基因调控和生物衰老的影响 定量外周基因表达和DNA甲基化的变化和老化。这一目标将扩大 研究逆境和免疫基因调控对极端自然灾害的影响，并量化免疫系统衰老 在多个层面上。第二，我将测量社会逆境、实际年龄和性别对周边环境的影响。 基因表达和DNA甲基化以及衰老的速度。这一目标将提供洞察这些因素如何 影响免疫反应的异质性，并调节大飓风后的免疫老化。 总之，这些研究将为了解极端自然灾害如何影响免疫基因提供帮助。 监管以及几个相关的社会和人口因素如何塑造这些反应。拟议 这项工作将增加对自然灾害和免疫基因调控中断的研究， 引入社会人口统计学数据的整合，以评估免疫系统多个领域的异质性 衰老这项工作代表了一个令人难以置信的培训机会的研究员，并将提供宝贵的见解， 极端灾害如何导致健康状况不佳，以及谁最容易受到这些负面影响。

PROJECT SUMMARY Extreme adverse environmental events, such as major hurricanes, are associated with increased incidence and severity of a myriad of health problems. Intriguingly, many of these ailments are also more prevalent in older individuals–hinting that adversity and aging affect the immune system in similar ways. Together, this suggests that adverse experiences may accelerate immune system aging. Disruptions to immune gene regulation can persist for many years and are expected to be a particularly salient mechanism by which extreme natural disasters drive aging-associated health declines. Additionally, individuals exhibit extensive heterogeneity in their responses to adversity, and factors such as social adversity (i.e., socioeconomic status, social integration), chronological age, and sex have been linked to differential health outcomes following disaster. However, most studies to date have focused on opportunistically collected samples without baseline data, and none have investigated whether gene expression and DNA methylation are accelerated by extreme hurricanes and how social experiences, chronological age, and sex affect multiple domains of immune gene regulation and aging. The goal of the proposed research is to address these gaps by taking advantage of an unparalleled sample of rhesus macaques (Macaca mulatta) from the island of Cayo Santiago that recently experienced Hurricane Maria. Macaques are a well-established animal model for translational human aging research because they share many genetic, social, and immunological features with humans. Peripheral whole blood samples for RNA were collected annually from representative samples of juvenile and adult male and female macaques for three years immediately prior to (2014-2016) and one year after (2018) Hurricane Maria. Blood samples for DNA were collected from 2010-2016 and in 2018. I will use this unique opportunity to investigate the effects of Hurricane Maria and its aftermath on gene regulation and biological aging of the peripheral immune system by quantifying changes to and aging of peripheral gene expression and DNA methylation. This aim will extend studies of adversity and immune gene regulation to extreme natural disaster and quantify immune system aging at multiple levels. Second, I will measure the effects of social adversity, chronological age, and sex on peripheral gene expression and DNA methylation and pace of aging. This aim will provide insight into how these factors influence the heterogeneity in immune responses and modulate immune aging following a major hurricane. Together, these studies will provide insight into how extreme natural disasters impact immune gene regulation and how several pertinent social and demographic factors shape these responses. The proposed work will add to the growing body of research on natural disaster and immune gene regulatory disruptions and introduce the integration of socio-demographic data to evaluate heterogeneity in multiple domains of immune aging. This work represents an incredible training opportunity for the fellow and will provide valuable insight into how extreme disasters drive poor health outcomes and who is most vulnerable to these negative effects.